Medizinische Universität Graz - Research portal
Selected Publication:
Egger, T; Schuligoi, R; Wintersperger, A; Amann, R; Malle, E; Sattler, W.
Vitamin E (alpha-tocopherol) attenuates cyclo-oxygenase 2 transcription and synthesis in immortalized murine BV-2 microglia.
BIOCHEM J 2003 370: 459-467.
Doi: 10.1042/BJ20021358
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- Leading authors Med Uni Graz
- Sattler Wolfgang
- Co-authors Med Uni Graz
- Amann Rainer
- Malle Ernst
- Schuligoi Rufina
- Wintersperger Andrea
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- Abstract:
- One of the immediate early microglial genes that are up-regulated in response to proinflammatory stimuli is cyclo-oxygenase 2 (COX-2). In the present study, we have investigated the effects of alpha-tocopherol (alpha TocH), an essential constituent of the nervous system, on the activation of COX-2 in lipopolysaccharide (LPS)-stimulated mouse BV-2 microglia. In unstimulated BV-2 cells, COX-2 mRNA and protein were almost undetectable but were strongly up-regulated in response to LPS. Activation of COX-2 protein synthesis in LPS-stimulated BV-2 cells involved activation of the extracellular-signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathway and was sensitive to the protein kinase C (PKC) inhibitors staurosporine and chelerythrine, and the MAP kinase/ERK kinase 1/2 inhibitors PD98059 and U0126. Supplementation of BV-2 cells with alpha TocH before LPS stimulation resulted in pronounced up-regulation of protein phosphatase 2A (PP2A) activity, down-regulation of PKC activity, ERK1/2 phosphorylation and nuclear factor kappa B (NF kappa B) activation. As a result, COX-2 protein levels and prostaglandin E(2) production were significantly lower in alpha TocH-supplemented cells. The effects of alpha TocH on PKC activity could be reverted by calyculin A and okadaic acid, two PP inhibitors. In summary, our results suggest that alpha TocH activates microglial PP2A activity and thereby silences an LPS-activated PKC/ERK/NF kappa B signalling cascade resulting in significantly attenuated COX-2 protein synthesis. These in vitro results imply that alpha TocH could induce quiescence to pathways that are associated with acute or chronic inflammatory conditions in the central nervous system.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Line, Transformed -
- Cyclooxygenase 2 -
- Dinoprostone - metabolism
- Enzyme Activation - physiology
- Isoenzymes - biosynthesis
- Lipopolysaccharides - metabolism
- Mice - metabolism
- Microglia - drug effects
- Mitogen-Activated Protein Kinases - metabolism
- NF-kappa B - metabolism
- Phosphoprotein Phosphatase - metabolism
- Prostaglandin-Endoperoxide Synthases - biosynthesis
- Vitamin E - metabolism
- Find related publications in this database (Keywords)
- extracellular signal-regulated kinase
- mitogen-activated protein kinase
- nuclear factor kappa B
- prostaglandin E-2